It is known that there is a variety of techniques for preparing pharmaceuticals, such as flurbiprofen, indoprofen, pirprofen, and the like. Moreover, as shown by U.S. Pat. No. 3,868,391 (Carney et al. I) and U.S. Pat. No. 4,239,901 (Rainer) and by Carney et al., Experientia, Vol. 29, page 938, 1973 (Carney et al. II), it is also known that some of these pharmaceuticals can be prepared via halonitrobenzeneacetic acids and derivatives thereof. A disadvantage of these known techniques of preparing pharmaceuticals and pharmaceutical intermediates has been their being tedious and time-consuming.
Golinski et al., Tetrahedron Letters, No. 37, pp. 3495-3498 (1978); Makosza et al., Journal of Organic Chemistry, 1980, Vol. 45, pp. 1534-1535; and Makosza, Int. Conf. Chem. Biotechnol. Biol. Act. Nat. Prod. (Proc.), 1st, 1981, Issue 2, pp. 480-490, teach nucleophilic substitution processes wherein nitroaromatic compounds are reacted with various nucleophiles, such as the alpha-halosulfones and N,N-dialkyl-1-haloalkanesulfonamides of Golinski et al., the alpha-substituted acetonitriles of Makosza et al., and the methyl alpha-phenylthioacetate, etc., of Makosza. Makosza, summarizing what he learned from the studies reported in these three articles, teaches on pages 484-485 that (1) a requirement for the operability of a nucleophile in these processes is that it be a CH acid that does not react rapidly with its carbanion--a carbanion having the general structure: ##STR1## wherein X is a leaving group, Y is a carbanion stabilizing group, and R is H, alkyl, aryl, etc., and in which the three variables must be properly combined and (2) CH acids in which X is halogen generally do not meet this requirement. Makosza et al. show that the operability of such nucleophiles is also dependent on the particular nitroaromatic compound used.